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PXD044499-1

PXD044499 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIrisin reduces Amyloid-β by inducing the release of neprilysin from astrocytes following downregulation of ERK-STAT3 signaling
DescriptionA pathological hallmark of Alzheimer’s disease (AD) is the deposition of amyloid-β protein (Aβ) in the brain. Physical exercise has been shown to reduce Aβ burden in various AD mouse models, but the underlying mechanisms have not been elucidated. Irisin, an exercise-induced hormone, is the secreted form of fibronectin-domain III containing 5 (FNDC5). Here, using a three-dimensional (3D) cell culture model of AD, we show that irisin significantly reduces Aβ pathology by increasing astrocytic release of the Aβ-degrading enzyme neprilysin (NEP). This is mediated by downregulation of ERK-STAT3 signaling. Finally, we show that integrin αV/β5 acts as the irisin receptor on astrocytes required for irisin-induced release of astrocytic NEP, leading to clearance of Aβ. Our findings reveal for the first time a cellular and molecular mechanism by which exercise-induced irisin attenuates Aβ pathology, suggesting a new target pathway for therapies aimed at the prevention and treatment of AD.
HostingRepositoryiProX
AnnounceDate2023-08-11
AnnouncementXMLSubmission_2023-09-07_19:22:49.875.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEunhee Kim
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-08-10 21:58:53ID requested
12023-09-07 19:22:50announced
22024-05-22 20:02:10announced2024-05-23: Update information.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Irisin, Alzheimer's disease, Astrocytes, Neprilysin, ERK, STAT3
Contact List
Se Hoon Choi
contact affiliationMassachusetts General Hospital
contact emailchoi.sehoon@mgh.harvard.edu
lab head
Eunhee Kim
contact affiliationMassachusetts General Hospital
contact emailekim43@mgh.harvard.edu
dataset submitter
Full Dataset Link List
iProX dataset URI